Conventionally, squalamine has been extracted from the livers of dogfish sharks. Due to the extremely low extraction efficiency of 0.001–0.002 wt %, chemical synthesis methods thereof have been investigated. As chemical synthesis methods of squalamine, (1) a method using 3β-acetoxy-5-cholanic acid as a starting material [see Tetrahedron Lett., Vol. 35, p. 8103 (1994)], (2) a method using 3β-hydroxy-5-cholanic acid as a starting material [see J. Org. Chem., Vol. 60, p. 5121 (1995); WO 94/19366], (3) a method using 21-hydroxy-20-methyl-pregn-4-en-3-one as a starting material [see WO98/24800; Org. Lett., Vol. 2, p. 2921 (2000)] and (4) a method using stigmasterol as a starting material [see J. Org. Chem., Vol. 63, p. 3786 (1998); J. Org. Chem., Vol. 63, p. 8599 (1998); WO 98/24800] are known.
The 3β-acetoxy-5-cholanic acid, 3β-hydroxy-5-cholanic acid and 21-hydroxy-20-methyl-pregn-4-en-3-one used as starting materials in the above-mentioned method (1), method (2) and method (3), respectively, are all expensive. Moreover, reaction operations are complicated in that 17 steps are required in the above-mentioned method (1) and 19 steps are required in method (2) to obtain squalamine and the like. Therefore, these methods can be hardly said to be industrially advantageous production methods of squalamine.
On the other hand, in the above-mentioned method (4), stigmasterol used as a starting material can be obtained at a low price, but 20 steps are required to synthesize squalamine. Moreover, method (4) is associated with problems in that silver carbonate used in the step to selectively oxidize hydroxyl group at the 3-position is expensive, a special reaction equipment is necessary because an ozone oxidation step at a low temperature is included and the like, and cannot necessarily be said to be an industrially advantageous method, either.
It is therefore an object of the present invention to provide a compound useful as a synthetic intermediate for a pharmaceuticals such as squalamine and the like.
Another object of the present invention is to provide a method capable of efficient production of the above-mentioned compound at high purity from an easily available starting material.